Title

Author

Date of Award

1-1-2009

Document Type

Campus Access Dissertation

Department

Pharmacology, Physiology and Neuroscience

Sub-Department

Biomedical Science

First Advisor

Alex McDonald

Abstract

The basolateral nuclear complex of the amygdala (BLC) receives a dense dopaminergic innervation that plays a critical role in the formation of emotional memory. Dopamine has been shown to influence the activity of BLC GABAergic interneurons, which differentially control the activity of pyramidal cells. However, little is known about how dopaminergic inputs interface with different interneuronal subpopulations in this region. To address this question, dual-labeling immunohistochemical techniques were used at the light and electron microscopic levels to examine inputs from tyrosine hydroxylase-immunoreactive (TH+) dopaminergic terminals to two different interneuronal populations in the rat basolateral nucleus labeled using antibodies to parvalbumin (PV) or calretinin (CR). In sections dual-labeled for TH/PV, 59% of the contacts of TH+ terminals with PV+ neurons were synapses, whereas in sections dual-labeled for TH/CR, only 13% of the contacts of TH+ terminals with CR+ cells were synapses. In separate preparations examined in complete serial sections for TH+ basket-like innervation of PV+ perikarya, most (76.2%) of TH+ terminal contacts with PV+ perikarya were synapses. These findings suggest that PV+ interneurons, but not CR+ interneurons, are prominent synaptic targets of dopaminergic terminals in the BLC.

DA receptor activation enhances sensory cortical inputs to the BLC involved in fear conditioning, while suppressing input from the medial prefrontal cortex (mPFC). DA releases mPFC inhibition of the BLC, in part, through hyperpolarization of neurons in the intercalated nuclei (ICN), which also receive DA and mPFC innervation. Phaseolus vulgaris leucoagglutinin (PHA-L) anterograde tract-tracer was injected into the temporal cortical area 3 (TCx), perirhinal/entorhinal (RCx), or the mPFC. Electron microscopic analysis of the BLp revealed that 54.1% [53/98] of RCx synapses were in the vicinity of TH-immunoreactive (-ir) axons. However, RCx and TH-ir axons were rarely (9.4% [5/53]) apposed to the same dendrites, suggesting that DA modulates RCx inputs primarily via extrasynaptic mechanisms. The lateral ICN is primarily innervated by RCx/TCx afferents. Selective innervation of the ICNs by mPFC and RCx/TCx excitatory afferents, and their neuromodulation by dopamine, have important implications in mediating feedforward inhibition of amygdala activity.